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1.
Small Methods ; : e2301579, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433396

RESUMO

Poly(ethylene oxide) (PEO)-based solid polymer electrolytes (SPEs) are widely utilized in all-solid-state sodium metal batteries (ASSSMBs) due to their excellent flexibility and safety. However, poor ionic conductivity and mechanical strength limit its development. In this work, an emerging solvent-free hot-pressing method is used to prepare mechanically robust PEO-based SPE, while sodium superionic conductors Na3 Zr2 Si2 PO12 (NZSP) and NaClO4 are introduced to improve ionic conductivity. The as-prepared electrolyte exhibits a high ionic conductivity of 4.42 × 10-4 S cm-1 and a suitable electrochemical stability window (4.5 V vs Na/Na+ ). Furthermore, the SPE enables intimate contact with the electrode. The Na||Na3 V2 (PO4 )3 @C ASSSMB delivers a high-capacity retention of 97.1% after 100 cycles at 0.5 C and 60 °C, and exhibits excellent Coulombic efficiency (CE) (close to 100%). The ASSSMB with the 20 µm thick electrolyte also demonstrates excellent cyclic stability. This study provides a promising strategy for designing stable polymer-ceramic composite electrolyte membranes through hot-pressing to realize high-energy-density sodium metal batteries.

2.
Microbiol Spectr ; 12(4): e0404223, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38442003

RESUMO

Azole drugs are the main therapeutic drugs for invasive fungal infections. However, azole-resistant strains appear repeatedly in the environment, posing a major threat to human health. Several reports have shown that mitochondria are associated with the virulence of pathogenic fungi. However, there are few studies on the mechanisms of mitochondria-mediated azoles resistance. Here, we first performed mitochondrial proteomic analysis on multiple Candida species (Candida albicans, Nakaseomyces glabrata, Pichia kudriavzevii, and Candida auris) and analyzed the differentially expressed mitochondrial proteins (DEMPs) between azole-sensitive and azole-resistant Candida species. Subsequently, we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene ontology analysis, and protein-protein interaction network analysis of DEMPs. Our results showed that a total of 417, 165, and 25 DEMPs were identified in resistant C. albicans, N. glabrata, and C. auris, respectively. These DEMPs were enriched in ribosomal biogenesis at cytosol and mitochondria, tricarboxylic acid cycle, glycolysis, transporters, ergosterol, and cell wall mannan biosynthesis. The high activations of these cellular activities, found in C. albicans and C. auris (at low scale), were mostly opposite to those observed in two fermenter species-N. glabrata and P. kudriavzevii. Several transcription factors including Rtg3 were highly produced in resistant C. albicans that experienced a complex I activation of mitochondrial electron transport chain (ETC). The reduction of mitochondrial-related activities and complex IV/V of ETC in N. glabrata and P. kudriavzevii was companying with the reduced proteins of Tor1, Hog1, and Snf1/Snf4.IMPORTANCECandida spp. are common organisms that cause a variety of invasive diseases. However, Candida spp. are resistant to azoles, which hinders antifungal therapy. Exploring the drug-resistance mechanism of pathogenic Candida spp. will help improve the prevention and control strategy and discover new targets. Mitochondria, as an important organelle in eukaryotic cells, are closely related to a variety of cellular activities. However, the role of mitochondrial proteins in mediating azole resistance in Candida spp. has not been elucidated. Here, we analyzed the mitochondrial proteins and signaling pathways that mediate azole resistance in Candida spp. to provide ideas and references for solving the problem of azole resistance. Our work may offer new insights into the connection between mitochondria and azoles resistance in pathogenic fungi and highlight the potential clinical value of mitochondrial proteins in the treatment of invasive fungal infections.


Assuntos
Candida , Infecções Fúngicas Invasivas , Humanos , Candida/genética , Candida/metabolismo , Azóis/farmacologia , Azóis/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Proteômica , Farmacorresistência Fúngica/genética , Candida albicans/metabolismo , Transdução de Sinais , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/farmacologia , Testes de Sensibilidade Microbiana
3.
Adv Mater ; : e2312879, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444241

RESUMO

Monodispersed microspheres play a major role in optical science and engineering, providing ideal building blocks for structural color materials. However, the method toward high solid content (HSC) monodispersed microspheres has remained a key hurdle. Herein, a facile access to harvest monodispersed microspheres based on the emulsion polymerization mechanism is demonstrated, where anionic and nonionic surfactants are employed to achieve the electrostatic and steric dual-stabilization balance in a synergistic manner. Monodispersed poly(styrene-butyl acrylate-methacrylic acid) colloidal latex with 55 wt% HSC is achieved, which shows an enhanced self-assembly efficiency of 280% compared with the low solid content (10 wt%) latex. In addition, Ag-coated colloidal photonic crystal (Ag@CPC) coating with near-zero refractive index is achieved, presenting the characteristics of metamaterials. And an 11-fold photoluminescence emission enhancement of CdSe@ZnS quantum dots is realized by the Ag@CPC metamaterial coating. Taking advantage of high assembly efficiency, easily large-scale film-forming of the 55 wt% HSC microspheres latex, robust Ag@CPC metamaterial coatings could be easily produced for passive cooling. The coating demonstrates excellent thermal insulation performance with theoretical cooling power of 30.4 W m-2, providing practical significance for scalable CPC architecture coatings in passive cooling.

4.
Sci Rep ; 14(1): 2863, 2024 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311664

RESUMO

Evidence regarding the association between dietary niacin intake and chronic obstructive pulmonary disease (COPD) is limited. Our study investigates the relationship between dietary niacin intake and the prevalance and incidence of COPD in the adult population of the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Data on niacin intake were extracted through dietary intake interviews. COPD diagnoses were based on lung function, medical history, and medication usage. We analyzed the association between niacin consumption and COPD using multiple logistic regression and restricted cubic spline models. The study included 7055 adult participants, divided into COPD (n = 243; 3.44%) and non-COPD (n = 6812; 96.56%) groups. Those with COPD had lower average niacin intake (21.39 ± 0.62 mg/day) compared to the non-COPD group (25.29 ± 0.23 mg/day, p < 0.001). In the adjusted multivariable model, the odds ratios (OR) and 95% confidence intervals (CI) for COPD in the highest versus lowest quartile of dietary niacin intake were 0.55 (0.33 to 0.89, P for trend = 0.009). Subgroup analysis, after adjustment for various variables, revealed no significant interaction effects. Dietary niacin intake was inversely associated with COPD prevalence in US adults. Participants with the highest dietary niacin intake demonstrated the lowest odds of COPD. The potential of dietary niacin supplementation as a strategy to mitigate COPD warrants further investigation.


Assuntos
Niacina , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Incidência , Prevalência , Dieta , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Ingestão de Alimentos
5.
RSC Adv ; 14(7): 4734-4741, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38318611

RESUMO

A series of hierarchical mordenite (MOR) catalysts were synthesized by adding soft templates via the solvent-free method. The influence of different kinds of soft templates on the structure, morphology and acid sites of mordenite were systematically characterized. The characterization results revealed that the addition of soft templates could successfully introduce hierarchical structure into the system while maintaining good crystallinity. The specific surface area and pore volume became larger. Surfactants could also affect the amount and distribution of acid sites, which in turn would affect the dimethyl ether carbonylation activity. Compared with cationic and nonionic surfactants, the addition of anionic surfactants such as sodium dodecyl benzene sulfonate could result in more Al species to preferentially enter into the 8 member ring, thus enhancing the amount of active sites for the carbonylation reaction while weakening the strength. Meanwhile, the addition of sodium dodecyl benzene sulfonate could also reduce the number of strong acid sites in the 12 member ring and obviously improve the carbonylation performance.

6.
J Matern Fetal Neonatal Med ; 37(1): 2250045, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38403928

RESUMO

BACKGROUND: The purpose of this study was to improve diagnostic and therapeutic standards by examining the clinical features, treatment, and prognosis of fetal meconium peritonitis (FMP), as well as the diagnostic efficacy of ultrasound for FMP. METHODS: The clinical data of 41 infants and pregnant women diagnosed with meconium peritonitis (MP) and treated at the Fujian Maternal and Child Health Hospital from January 2013 to January 2020 were analyzed retrospectively. Clinical data, imaging data, complications, treatment strategies, pregnancy outcomes, neonatal prognoses, and follow-up outcomes were all analyzed. RESULTS: The MP prenatal diagnosis rate was 56.1% (23/41), the neonatal surgery rate was 53.7% (22/41), and the survival rate was 85.4% (35/41). Intraperitoneal calcification (23 pregnant women, 56.1%), intestinal dilatation (13 pregnant women, 31.7%), peritoneal effusion (22 pregnant women, 53.7%), intraperitoneal pseudocyst (7 pregnant women, 17.1%), and polyhydramnios were diagnosed via prenatal ultrasound (18 pregnant women, 43.9%). Twenty-two pregnant women were assigned to the surgical treatment (operation) group, while 18 were assigned to the conservative treatment group. In the operation group, there were 9 cases of ileal atresia (40.9%), 7 cases of jejunal atresia (31.8%), 2 cases of atresia at the jejunum-ileum junction (9.1%), 2 cases of ileal perforation (9.1%), 1 case of ileal necrosis (4.5%), and 1 case of adhesive obstruction (4.5%). There was no statistically significant difference (p > .05) in the occurrence of various prenatal ultrasound findings by etiology. CONCLUSION: Multiple prenatal ultrasound markers have been identified for MP. To improve the efficacy of newborn treatment for FMP and reduce neonatal mortality, dynamic monitoring of ultrasound image alterations and strengthened integrated perinatal management are necessary.


Assuntos
Perfuração Intestinal , Peritonite , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Perfuração Intestinal/diagnóstico por imagem , Perfuração Intestinal/cirurgia , Mecônio , Peritonite/diagnóstico , Peritonite/terapia , Peritonite/etiologia , Estudos Retrospectivos , Ultrassonografia Pré-Natal
7.
Biomed Pharmacother ; 171: 116112, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171246

RESUMO

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS) and peroxidation of membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). Ferroptosis is unique among other cell death modalities in many aspects. It is initiated by excessive oxidative damage due to iron overload and lipid peroxidation and compromised antioxidant defense systems, including the system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway and the GPX4-independent pathways. In the past ten years, ferroptosis was reported to play a critical role in the pathogenesis of various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, and myocardial ischemia-reperfusion injury. Studies have identified dysfunctional iron metabolism and abnormal expression profiles of ferroptosis-related factors, including iron, GSH, GPX4, ferroportin (FPN), and SLC7A11 (xCT), as critical indicators for atherogenesis. Moreover, ferroptosis in plaque cells, i.e., vascular endothelial cell (VEC), macrophage, and vascular smooth muscle cell (VSMC), positively correlate with atherosclerotic plaque development. Many macromolecules, drugs, Chinese herbs, and food extracts can inhibit the atherogenic process by suppressing the ferroptosis of plaque cells. In contrast, some ferroptosis inducers have significant pro-atherogenic effects. However, the mechanisms through which ferroptosis affects the progression of AS still need to be well-known. This review summarizes the molecular mechanisms of ferroptosis and their emerging role in AS, aimed at providing novel, promising druggable targets for anti-AS therapy.


Assuntos
Aterosclerose , Ferroptose , Hiperaldosteronismo , Placa Aterosclerótica , Humanos , Glutationa , Ferro , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio
8.
Kaohsiung J Med Sci ; 40(2): 150-160, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38088510

RESUMO

Tumor necrosis factor receptor-associated factor 5 (TRAF5) has been implicated in the pathogenesis of human malignancies. This work aimed to clarify the role of TRAF5 in lung adenocarcinoma (LUAD) progression. Herein, we uncovered that TRAF5 level was reduced in LUAD tissues. Low TRAF5 expression correlated with dismal prognosis in LUAD patients. Moreover, upregulated TRAF5 impeded cell viability, migration, and invasion, induced apoptosis in vitro, as well as impaired tumorigenicity in vivo. However, depletion of TRAF5 revealed opposing results. Moreover, TRAF5 was identified as the downstream target of methyltransferase-like 3 (METTL3)-elicited N6 -methyladenosine (m6 A) modification. METTL3 stabilized TRAF5 mRNA and positively modulated TRAF5 level. Further, TRAF5 depletion relieved the repressive phenotype caused by METTL3 addition. In addition, it was manifested that the METTL3/TRAF5 axis served as an inhibitor in LUAD through the PI3K/AKT/Nuclear Factor-Kappa B (NF-κB) signaling. Collectively, we propose that METTL3-mediated TRAF5 m6 A modification exerted as a vital tumor inhibitory function in LUAD development. The METTL3/TRAF5 axis may be a critical effector of LUAD progression.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator 5 Associado a Receptor de TNF/genética , Fator 5 Associado a Receptor de TNF/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Transdução de Sinais/genética , Metilação , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/genética
9.
Environ Pollut ; 342: 123104, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070645

RESUMO

Reservoirs play important roles in the drinking water supply for urban residents, agricultural water provision, and the maintenance of ecosystem health. Satellite optical remote sensing of water quality variables in medium and micro-sized inland waters under oligotrophic and mesotrophic status is challenging in terms of the spatio-temporal resolution, weather conditions and frequent nutrient status changes in reservoirs, etc., especially when quantifying non-optically active components (non-OACs). This study was based on the surface reflectance products of unmanned aerial vehicle (UAV) multispectral images, Sentinel-2B Multispectral instrument (MSI) images and Landsat 7 Enhanced Thematic Mapper Plus (ETM+) by utilizing fuzzy C-means (FCM) clustering algorithm was combined with band combination (BC) model to construct the FCM-BC empirical model, and used mixed density network (MDN), extreme gradient boosting (XGBoost), deep neural network (DNN) and support vector regression (SVR) machine learning (ML) models to invert 12 kinds of optically active components (OACs) and non-OACs. Compared with the unclustered BC (UC) model, the mean coefficient of determination (MR) of the FCM-BC models was improved by at least 46.9%. MDN model showed best accuracy (R2 in the range of 0.60-0.98) and stability (R2 decreased by up to 13.2%). The accuracy of UAV was relatively higher in both empirical methods and machine learning methods. Additionally, the spatio-temporal distribution maps of four water quality variables were mapped based on the MDN model and UAV images, all platforms showed good consistency. An inversion strategy of water quality variables in various monitoring frequencies and weather conditions were proposed finally. The purpose of introducing the UAV platform was to cooperate with the satellite to improve the monitoring response ability of OACs and non-OACs in small and micro-sized oligotrophic and mesotrophic water bodies.


Assuntos
Tecnologia de Sensoriamento Remoto , Qualidade da Água , Ecossistema , Abastecimento de Água , China
10.
J Dig Dis ; 24(12): 691-701, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37994615

RESUMO

OBJECTIVE: To estimate the performance of the FibroTouch-based ultrasound attenuation parameter (UAP) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD), with magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. METHODS: This prospective, cross-sectional study included 275 individuals in the training group and 110 individuals in the validation group, all of whom completed a standardized research visit, laboratory tests, MRI-PDFF, and UAP measurements over 1 month. Pearson correlation coefficient and Bland-Altman analysis were used to assess the agreement between UAP and MRI-PDFF for the detection of hepatic steatosis. The diagnostic value of UAP was evaluated by the area under the receiver operating characteristic (ROC) curve (AUROC). Confounding factors to UAP performance were identified by ROC curves and regression analyses. RESULTS: The AUROC of UAP for detecting MRI-PDFF at ≥5%, ≥10%, and ≥20% were 0.95 (95% confidence interval [CI] 0.92-0.97), 0.86 (95% CI 0.81-0.90), and 0.90 (95% CI 0.86-0.93), respectively, and their optimal thresholds were 259, 274, and 295 dB/m, respectively. The UAP measurements had higher diagnostic accuracy in participants with lower waist circumference (≤90 cm for men and ≤80 cm for women) compared to those with higher waist circumference (AUROC values: 0.97 vs 0.84, P < 0.05). Bland-Altman analysis showed good agreement between UAP and MRI-PDFF (bias 0.00021). According to established regression analyses, hepatic steatosis could be accurately diagnosed using UAP estimation. CONCLUSIONS: FibroTouch-UAP has a high diagnostic potential for hepatic steatosis in NAFLD patients and helps clinical assessment and monitoring.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/patologia , Estudos Transversais , Estudos Prospectivos , Curva ROC , Imageamento por Ressonância Magnética/métodos , Padrões de Referência
11.
Medicine (Baltimore) ; 102(45): e35879, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37960783

RESUMO

Panvascular diseases are a group of vascular system diseases, mainly including the heart, brain, neck, and other parts of the vascular lesions. As a non-pharmacological intervention, exercise therapy could prevent and treat Panvascular diseases. However, few bibliometric analyses of exercise therapy in Panvascular disease exist. This study aimed to analyze the trends and hotspots over the past decade and provide insights into the latest state of the art in global research, thereby contributing to further research in the field. We systematically searched the Web of Science Core Collection (WOSCC) for articles on exercise therapy and Panvascular disease. The acquired information from the reports was analyzed using CiteSpace and VOSviewer software to assess and forecast this field hottest areas and trends. The final analysis included 294 articles by our specified inclusion criteria. The number of publications has gradually increased over the past decade. Stroke was one of the most studied Panvascular diseases. China and the University of Sao Paulo were the country es and institutions that contributed the most to the field. Mary M. McDermott was the most prolific researcher, and the Journal of Vascular Surgery published the most articles. The 6-minute walk test, skeletal muscle, oxidative stress, and supervised exercise therapy were hot topics from 2019 to 2023. In conclusion, exploring exercise therapy programs and exercise mechanisms for Panvascular diseases has been ongoing. This study revealed the current status and trends of research in the field and identified hot topics. It was helpful for scholars to understand exercise therapy critical role in treating and preventing Panvascular diseases and provided a reference for clinical decision-making and further research.


Assuntos
Terapia por Exercício , Exercício Físico , Humanos , Bibliometria , Encéfalo , China
12.
ACS Chem Neurosci ; 14(19): 3674-3685, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37718490

RESUMO

Patients with post-traumatic stress disorder (PTSD) usually manifest persistence of the traumatic memory for a long time after the event, also known as resistance to extinction learning. Numerous studies have shown that the endocannabinoid system, specifically the cannabinoid type-1 receptor (CB1R), plays an important role in traumatic memory. However, the effect of basolateral amygdala (BLA) CB1R in social fear memory formation and elimination is still unclear. Here, we built a mouse model of social avoidance induced by acute social defeat stress to investigate the role of BLA CB1R in social fear memory formation and anxiety- and depression-like behavior. Anterograde knockout of CB1R in BLA neurons facilitates social fear memory formation and manifests an anxiolytic effect but does not influence sociability and social novelty. Retrograde knockout of CB1R in BLA promotes social fear memory formation and shows an anxiogenic effect but does not affect sociability and social novelty. Moreover, intracerebral injection of the CB1R antagonist AM251 in BLA during the memory reconsolidation time window eliminates social fear memory. Our findings suggest the CB1R of BLA can be used as a novel molecular target in social fear memory formation and elimination and potential PTSD therapy with memory retrieval and AM251.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Canabinoides , Animais , Camundongos , Humanos , Canabinoides/farmacologia , Receptor CB1 de Canabinoide/genética , Medo , Ansiedade , Extinção Psicológica
13.
Int J Biol Macromol ; 253(Pt 4): 126953, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37734516

RESUMO

Long intergenic non-coding RNA 00657 (linc00657) is involved in various diseases, whereas its role in atherosclerosis (AS) development remains inconclusive. This study was designed to investigate the effects and underlying mechanisms of linc00657 in atherogenesis. The results showed that ox-LDL treatment significantly induced pyroptosis in human THP-1-derived macrophages. The secretion levels of LDH and pro-inflammatory factors were markedly enhanced, and the integrity of plasma membranes was disrupted in ox-LDL-treated THP-1-derived macrophages. These effects were significantly compensated after transfection with linc00657 siRNA and became more evident by linc00657 overexpression. Moreover, the effects of linc00657 overexpression on pyroptosis of THP-1-derived macrophages can also be robustly reversed by TXNIP knockdown or miR-106b-5p mimics transfection. Mechanistically, linc00657 enhanced TXNIP expression by competitively binding to miR-106b-5p, promoting NLRP3 inflammasome activation. Finally, we found that linc00657 overexpression significantly increased the expression of pyroptosis-related factors and decreased miR-106b-5p level in the aorta of high-fat-diet-fed apoE-/- mice. Furthermore, linc00657 up-regulation enlarged the plaque area, exacerbated plasma lipid profile, and increased pro-inflammatory cytokines levels in the serum, effects that were reversed by injection of miR-106b-5p agomir. This evidence indicated that linc00657 stimulated macrophage pyroptosis and aggravated the progression of AS via the miR-106b-5p/TXNIP/NLRP3 pathway.


Assuntos
Aterosclerose , MicroRNAs , Humanos , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/genética , Macrófagos/metabolismo , Aterosclerose/metabolismo , Proteínas de Transporte/metabolismo
14.
Mol Med Rep ; 28(3)2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37449516

RESUMO

N6-methyl-adenosine (m6a) is involved in the occurrence and development of various diseases such as autogenic immune disease and tumors. Methyltransferases regulate primary (pri)-microRNA (miRNA/miR) processing by mediating m6a modifications, consequently affecting pathological processes including immune-related diseases by regulating both innate and adaptive immune cells. However, the roles of m6a on the biological functions of bone marrow mesenchymal stem cells (BMSCs) remain to be elucidated. The relative expression levels of methyltransferase-like 14 (METTL14) and other methyltransferases, demethylases, and miR-873 in bone samples from patients with osteoporosis and from normal individuals were measured by reverse transcription-quantitative PCR. Cell Counting Kit-8 assay was used to examine the proliferation of BMSCs. Co-immunoprecipitation (Co-IP) was used to investigate the binding of METTL14 to DiGeorge syndrome critical region 8 (DGCR8). RNA immunoprecipitation (RIP) was used to examine the binding of METTL14 to pri-miR-873. METTL14 and m6a modifications were highly detected in patients with osteoporosis compared with the controls. Co-IP results indicated that silencing of METTL14 reduced METTL14 and m6a modification levels in BMSCs. Downregulation of METTL14 significantly promoted the proliferation of BMSCs. RIP results suggested that METTL14/m6a methylation modification promoted the processing of pri-miR-873 by binding to DGCR8 in BMSCs. Furthermore, overexpression of miR-873 inhibited the proliferation of BMSCs. The results also showed that miR-873 mimics significantly inhibited the proliferation in small interfering (si)-METTL14 transfected BMSCs; however, miR-873 inhibitors markedly promoted the proliferation of si-METTL14 transfected BMSCs. METTL14 and m6a modifications were upregulated in osteoporosis samples. METTL14 promoted the processing of pri-miR-873 into mature miR-873 by regulating m6a modification. Furthermore, overexpression of miR-873 significantly inhibited the proliferation of BMSCs. Therefore, the METTL14/m6a/miR-873 axis may be a potential target for the treatment of osteoporosis.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Osteoporose , Humanos , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/metabolismo , Diferenciação Celular/genética , Osteogênese/genética , Osteoporose/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proliferação de Células/genética , Células da Medula Óssea , Metiltransferases/genética , Metiltransferases/metabolismo
15.
J Neuropathol Exp Neurol ; 82(9): 806-813, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37478479

RESUMO

Neuropathic pain has a complex pathogenesis. Here, we examined the role of caveolin-1 (Cav-1) in the anterior cingulate cortex (ACC) in a chronic constriction injury (CCI) mouse model for the enhancement of presynaptic glutamate release in chronic neuropathic pain. Cav-1 was localized in glutamatergic neurons and showed higher expression in the ACC of CCI versus sham mice. Moreover, the release of glutamate from the ACC of the CCI mice was greater than that of the sham mice. Inhibition of Cav-1 by siRNAs greatly reduced the release of glutamate of ACC, while its overexpression (induced by injecting Lenti-Cav-1) reversed this process. The chemogenetics method was then used to activate or inhibit glutamatergic neurons in the ACC area. After 21 days of injection of AAV-hM3Dq in the sham mice, the release of glutamate was increased, the paw withdrawal latency was shortened, and expression of Cav-1 in the ACC was upregulated after intraperitoneal injection of 2 mg/kg clozapine N-oxide. Injection of AAV-hM4Di in the ACC of CCI mice led to the opposite effects. Furthermore, decreasing Cav-1 in the ACC in sham mice injected with rAAV-hM3DGq did not increase glutamate release. These findings suggest that Cav-1 in the ACC is essential for enhancing glutamate release in neuropathic pain.


Assuntos
Ácido Glutâmico , Neuralgia , Animais , Camundongos , Caveolina 1/genética , Caveolina 1/metabolismo , Ácido Glutâmico/metabolismo , Giro do Cíngulo/metabolismo , Neuralgia/metabolismo , Neuralgia/patologia , Neurônios/patologia
16.
J Environ Manage ; 342: 118099, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37207457

RESUMO

Tracking contaminants in karst aquifers is challenging because of the high heterogeneity encountered in carbonate rocks. Multi-tracer tests, combined with chemical and isotopic analyses, were conducted to solve a groundwater contamination incident within a complex karst aquifer in Southwest China. Results showed that: (1) the wastewater from a paper mill, public sewers, and septic tanks were the three main potential contaminant sources identified by chemical and isotopic methods; (2) a direct effect of the paper mill wastewater with high Na+ (up to 2230.5 mg/L) and chemical oxygen demand (COD) concentrations on spring water quality was confirmed by multi-tracer tests, which changed the water type from Ca-HCO3 in the 1970s to Ca-Na-HCO3 in the present study and resulted in a depleted carbon isotope value (-16.5‰); and (3) the studied aquifer is a highly complex karst system, due to two conduits crossed each other without mixing, contaminants traveled a long distance (up to 14 km) within the lower conduit, paper mill-contaminated groundwater flowed across a river bottom and discharged to the opposite bank, and an active subsurface divide occurred. After several months of operation, the groundwater restoration measure based on karst hydrogeologic conditions proved that cutting off contaminant sources for karst aquifer self-restore was effective in practice, which contributed to the decline in NH4+ (from 7.81 mg/L to 0.04 mg/L), Na+ (from 50.12 mg/L to 4.78 mg/L), and COD (from 16.42 mg/L to 0.9 mg/L) concentrations coupled with an increase in δ13C-DIC value (from -16.5‰ to -8.4‰) in the earlier contaminated karst spring. This study's integrated method is expected to screen and confirm contaminant sources within complex karst systems rapidly and effectively, thereby contributing to karst groundwater environmental management.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Rios , Águas Residuárias , Poluentes Químicos da Água/análise , Água Subterrânea/análise , Isótopos de Carbono/análise
17.
Eur J Radiol ; 163: 110835, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37098281

RESUMO

PURPOSE: Statistical photon noise has always been a common problem in X-ray multi-contrast imaging and significantly influenced the quality of retrieved differential phase and dark-field images. We intend to develop a deep learning-based denoising algorithm to reduce the noise of retrieved X-ray differential phase and dark-field images. METHODS: A novel deep learning based image noise suppression algorithm (named DnCNN-P) is presented. We proposed two different denoising modes: Retrieval-Denoising mode (R-D mode) and Denoising-Retrieval mode (D-R mode). While the R-D mode denoises the retrieved images, the D-R mode denoises the raw phase stepping data. The two denoising modes are evaluated under different photon counts and visibilities. RESULTS: Experimental results show that with the algorithm DnCNN-P used, the D-R mode always exhibits a better noise reduction under diverse experimental conditions, even in the case of a low photon count and/or a low visibility. With a detected photon count of 1800 and a visibility of 0.3, compared to the differential phase images without denoising, the standard deviation is reduced by 89.1% and 16.4% in the D-R and R-D modes. Compared to the dark-field images without denoising, the standard deviation is reduced by 83.7% and 12.6% in the D-R and R-D modes, respectively. CONCLUSIONS: The novel supervised DnCNN-P algorithm can significantly reduce the noise in retrieved X-ray differential phase and dark-field images. We believe this novel algorithm can be a promising approach to improve the quality of X-ray differential phase and dark-field images, and therefore dose efficiency in future biomedical applications.


Assuntos
Aprendizado Profundo , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Raios X , Razão Sinal-Ruído , Radiografia , Algoritmos , Processamento de Imagem Assistida por Computador/métodos
18.
CNS Neurosci Ther ; 29(7): 1940-1952, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36914579

RESUMO

AIMS: The aim was to investigate the effect of mood disorders on parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor disability, substantia nigra pars compacta (SNc) dopaminergic (DA) neurons loss. Also, the neural circuit mechanism was elucidated. METHODS: The depression-like (physical stress, PS) and anxiety-like (emotional stress, ES) mouse models were established by the three-chamber social defeat stress (SDS). The features of Parkinson's disease were reproduced by MPTP injection. Viral-based whole-brain mapping was utilized to resolve the stress-induced global changes in direct inputs onto SNc DA neurons. Calcium imaging and chemogenetic techniques were applied to verify the function of the related neural pathway. RESULTS: We found that PS mice, but not ES mice, showed worse movement performance and more SNc DA neuronal loss than control mice after MPTP administration. The projection from the central amygdala (CeA) to the SNcDA was significantly increased in PS mice. The activity of SNc-projected CeA neurons was enhanced in PS mice. Activating or inhibiting the CeA-SNcDA pathway could mimic or block PS-induced vulnerability to MPTP. CONCLUSIONS: These results indicated that projections from CeA to SNc DA neurons contribute to SDS-induced vulnerability to MPTP in mice.


Assuntos
Pessoas com Deficiência , Transtornos Motores , Animais , Camundongos , Humanos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Substância Negra , Neurônios Dopaminérgicos/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
19.
J Ethnopharmacol ; 308: 116307, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36842722

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine and food, Euodiae Fructus (EF) is widely used in clinics to relieve pain and prevent vomiting and for making tea for more than a thousand years. In recent years, hepatotoxic reactions to EF have been reported. The intermediates produced by evodiamine and rutaecarpine metabolism in vitro were captured by glutathione (GSH), suggesting that the toxicity of EF may be related to metabolic activation. Whether licorice can inhibit the metabolic activation of EF has not been reported, which needed an effective strategy to clarify the correlation between protein conjugates and hepatotoxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: This study aimed to explore the toxic components and mechanisms of EF based on metabolic activation and the detoxification of licorice. MATERIALS AND METHODS: The content and toxicity index of protein conjugates in the liver were determined by orally administering mice and rats with EF. The attenuation mechanism of licorice was examined in cell and enzymology experiments. RESULTS: The change in evodiamine-cysteinylglycine (EVO-Cys-Gly) and evodiamine-cysteine (EVO-Cys) levels was consistent with the change in hepatotoxicity. Licorice inhibited the formation of the protein conjugates of EF and increased the content of GSH in L02 cells. CONCLUSION: EF mediated by P450 enzymes produced toxic intermediates, which combined with cysteine residues in animal liver and inactivate them, leading to hepatotoxicity. Interestingly, licorice can alleviate the GSH depletion caused by EF and inhibit the production of protein conjugates by inhibiting P450 enzymes.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Glycyrrhiza , Ratos , Camundongos , Animais , Cisteína , Sistema Enzimático do Citocromo P-450 , Glutationa/metabolismo
20.
Adv Mater ; 35(11): e2208065, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36719053

RESUMO

Phase-change memory (PCM) is one of the most promising candidates for next-generation data-storage technology, the programming speed of which has enhanced within a timescale from milliseconds to sub-nanosecond (≈500 ps) through decades of effort. As the potential applications of PCM strongly depend on the switching speed, namely, the time required for the recrystallization of amorphous chalcogenide media, the finding of the ultimate crystallization speed is of great importance both theoretically and practically. In this work, through systematic analysis of discovered phase-change materials and ab initio molecular dynamics simulations, elemental Sb-based PCM is predicted to have a superfast crystallization speed. Indeed, such cells experimentally present extremely fast crystallization speeds within 360 ps. Remarkably, the recrystallization process is further sped up as the device shrinks, and a record-fast crystallization speed of only 242 ps is achieved in 60 nm-size devices. These findings open opportunities for dynamic random-access memory (DRAM)-like and even cache-like PCM using appropriate storage materials.

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